Download doc Summer 2010 Lecture 2

5/4/2010
Lecture 2
Pedigrees
Have symbols
Children are indicated from L to R in the order of birth
- if prior relation, 2 lines connecting the mating pair
often used for diseases, but can be for any traits
CF:
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autosomal recessive
deals with ion regulation in membranes
o dysregulated ion transport
o excrete salt in larger than normal quantities
lungs and GI: because of salinity problems  mucous buildup in lungs that
won’t come out of lungs
o bacteria stay in mucous
single gene causes disease (CFTR)
can look at pedigrees to determine autosomal recessiveness:
o see 2 parents without trait, but children with the trait
o if several generations don’t have the trait but one generation does, is
probably recessive
 sometimes grandparents have disorder
o generations indicated in roman numerals top to bottom; everyone gets
a number 1+ from L to R
often tend to have common ancestry (consanguineous union)
males and females equally affected
must be able to look at pedigree to determine things
so if the kids have the phenotype but parents don’t, then must be heterozygous
o grandparents generation
Rare: can make assumptions:
o Heterozygous is most likely going to pick a homozygous dominant
mate (Aa will pick AA mate)
o Think 1 in 1 million
o Low possibility of being in the carrier population
A- means have at least 1 copy of dominant allele
III-1 has a ½ probability of being a carrier
o Father only gives A
o Mom can contribute either A or a
Genotypes of unaffected siblings in IV: IV-1’s probability of being a carrier
o Is a heterozygous cross
  is 2/3
o if had another child, risk of being carrier is ½
 risk of having recessive allele is ¾
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Autosomal dominant disorders
- e.g. Marfan syndrome
o CT tissue formation
o Tall, lanky, long fingers
- Different from before:
o Every generation shows the disorder
 Trait is most often expressed in every generation
o Males and females equally affected (same as before)
o If 1 parent affected and other isn’t, have 1:1 ratio of affected
- A = Marfan allele; a = WT
- Rare means heterozygous is more common than homozygous
o At best, in this pedigree, could be Aa because grandparent generation
has 1 unaffected
- Probability
o Next child of II-6 and II-7 will have Marfan
 ½
 II-7 can only produce “a” allele
 II-6 can produce both alleles
  ½ of progeny will have disorder
o Probability of II-1 and II-2 having Marfan’s kid
 0
o Probability of III-5 having a boy with Marfan syndrome
 ¼
 ½ probability of having Marfan, ½ probability of being a boy
 ¼ probability
 if it weren’t rare, can’t assume would meet someone without
the trait
Non-rare trait
- in this pedigree, see 3 generations with the trait
o however, not autosomal dominant because have taster parents with
non-taster child
o fairly equal distro between males and females; lots of people affected
o if allele not rare, people mating into the family may have the trait
- not rare = polymorphism (e.g. here, is a bimorphism)
Sex-linked pedigrees: X-linkage
- e.g. if rare trait
o is autosomal recessive?
 Skips generations
 Few people have it
 Not many females, but very few numbers
 If is rare, II-3 shouldn’t be a carrier
 But, if X-linked, mom could be a carrier and II-3 doesn’t have
to be heterozygous
 III-3 and -4 could be either carrier or not
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More males than females develop trait
Affected fathers don’t pass trait onto their sons because only providing a Y
chromosome
Affected father doesn’t normally pass trait onto any offspring normally
because is rare: mom not likely to have recessive/be carrier
Every son of a rare affected female will have trait
Every daughter of affected female will be a carrier
Dominant X-linked trait
o Affected males pass trait onto all daughters but none of his sons
 Because passes X to the females; Y onto males
 If rare, daughters likely to be heterozygous
Y-linked inheritance
- no females affected
- affected male passes trait to all his sons
Multiple Gene Inheritance 1
Independent assortment
- impt for agriculture
- “Mendel’s First Law”
o genes move evenly through generations
“Mendel’s Second Law”
- how genes move wrt each other
o dominant vs recessive
- 9:3:3:1 ratio
o indicative of a dihybrid cross
 2 heterozygotes
o if have a 1:1:1:1 ratio of the traits, end up with this ratio
- test cross: RrYy x rryy
o end up with a 1:1:1:1 ratio of round yellow, round grn, wrinkled ylw
and wrinkled grn
More complex crosses
- use branch diagrams
o can look at each gene at a time if genes are moving independently
- crossing 6 independently assorting genes, e.g.
o use the product rule
 multiply probabilities of independent events
Chi2 (2) test
- Null hypothesis: no real difference between observed and expected
o If seems statistically abnormal, reject the null
- Cleanest way to do this is:
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Know the 2 formula and how to use it
Df= a measure of the number of classes (e.g. flipping a coin: there are 2
classes—heads or tails)
o Df= n-1 = 2-1 = 1
Get a 2 distro
o 5% will fall in the tail
5% is the critical value for statistical significance
o p =< .05
if falls above the threshold (.05), can’t reject the null ( coin does flip
normally)
Example: flower colour controlled by partial dominance?
o WW x ww where W = red and w = white  all pink F1
o Test whether or not what is observed is what is expected
o Critical value 5.99 (chart given on exam)
 6.8>5.99  reject the null
Meiosis is the chromosomal basis of independent assortment
Polygenic traits
- continuously varying trait
- single trait controlled by 2 genes, in an additive manner, e.g.
- e.g. homozygous recessive would be colourless; each dominant allele added
on adds a dose of colour
o can end up with a normal distribution
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